Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

被引：275

作者：

Ding, Li ^{[1
,2
,3
,4
]}

Bailey, Matthew H. ^{[1
,2
]}

Porta-Pardo, Eduard ^{[5
,6
]}

Thorsson, Vesteinn ^{[7
]}

Colaprico, Antonio ^{[8
,9
]}

Bertrand, Denis ^{[10
]}

Gibbs, David L. ^{[7
]}

Weerasinghe, Amila ^{[1
,2
]}

Huang, Kuan-lin ^{[1
,2
]}

Tokheim, Collin ^{[11
,12
]}

Cortes-Ciriano, Isidro ^{[13
,14
,15
]}

Jayasinghe, Reyka ^{[1
,2
]}

Chen, Feng ^{[1
,4
]}

Yu, Lihua ^{[16
]}

Sun, Sam ^{[17
]}

Olsen, Catharina ^{[8
]}

Kim, Jaegil ^{[18
]}

Taylor, Alison M. ^{[18
,19
]}

Cherniack, Andrew D. ^{[18
,19
]}

Akbani, Rehan ^{[20
]}

Suphavilai, Chayaporn ^{[10
]}

Nagarajan, Niranjan ^{[10
]}

Stuart, Joshua M. ^{[21
]}

Mills, Gordon B. ^{[22
]}

Wyczalkowski, Matthew A. ^{[1
,2
]}

Vincent, Benjamin G. ^{[23
,24
]}

Hutter, Carolyn M. ^{[25
]}

Zenklusen, Jean Claude ^{[26
]}

Hoadley, Katherine A. ^{[23
,27
]}

Wendl, Michael C. ^{[1
,2
,3
]}

Shmulevich, Llya ^{[7
]}

Lazar, Alexander J. ^{[28
,29
,30
]}

Wheeler, David A. ^{[31
,32
,33
]}

Getz, Gad ^{[13
,18
,34
]}

机构：

[1] Washington Univ, Dept Med, St Louis, MO 63110 USA

[2] Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA

[3] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[4] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA

[5] Barcelona Supercomp Ctr, Barcelona 08034, Spain

[6] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA 92037 USA

[7] Inst Syst Biol, Seattle, WA 98109 USA

[8] Univ Libre Bruxelles, Dept Informat, MLG, B-1050 Brussels, Belgium

[9] Univ Miami, Dept Human Genet, Miami, FL 33136 USA

[10] Genome Inst Singapore, Computat & Syst Biol, Singapore 13862, Singapore

[11] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD 21218 USA

[12] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA

[13] Harvard Med Sch, Boston, MA 02115 USA

[14] Ludwig Ctr Harvard, Boston, MA 02115 USA

[15] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[16] H3 Biomed Inc, Cambridge, MA 02139 USA

[17] Baylor Coll Med, Dept Radiat Oncol, Houston, TX 77030 USA

[18] Broad Inst, Cambridge, MA 02142 USA

[19] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA

[20] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77498 USA

[21] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA

[22] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77498 USA

[23] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[24] Univ N Carolina, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC 27599 USA

[25] NHGRI, Bethesda, MD 20892 USA

[26] NCI, Bethesda, MD 20892 USA

[27] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[28] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77498 USA

[29] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77498 USA

[30] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77498 USA

[31] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[32] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[33] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[34] Massachusetts Gen Hosp, Boston, MA 02114 USA

来源：

CELL | 2018年 / 173卷 / 02期

关键词：

SOMATIC POINT MUTATIONS; DISCOVERY; CLASSIFICATION; EXPRESSION; BREAST; TUMORS; LANDSCAPE; DRIVER; IDENTIFICATION; INFORMATION;

D O I：

10.1016/j.cell.2018.03.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing.

引用

页码：305 / +

页数：26

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